To investigate the therapeutic effect of high-dosage gamma-aminobutyric acid (GABA) on acute tetramine (TET) poisoning, 50 Kunming mice were divided into 5 groups at random and the antidotal effects of GABA or sodium dimercaptopropane sulfonate (Na-DMPS) on poisoned mice in different groups were observed in order to compare the therapeutic effects of high-dosage GABA with those of Na-DMPS. Slices of brain tissue of the poisoned mice were made to examine pathological changes of cells. The survival analysis was employed. Our results showed that both high-dosage GABA and Na-DMPS could obviously prolong the survival time, delay onset of convulsion and muscular twitch, and ameliorate the symptoms after acute tetramine poisoning in the mice. Better effects could be achieved with earlier use of high dosage GABA or Na-DMPS. There was no significant difference in prolonging the survival time between high-dose GABA and Na-DMPS used immediately after poisioning. It is concluded that high-dosage GABA can effectively antagonize acute toxicity of teramine in mice. And it is suggested that high-dosage GABA may be used as an excellent antidote for acute TET poisoning in clinical practice. The indications and correct dosage for clinical use awaits to be further studied.
Acute Disease ; Antidotes/*administration & dosage ; Antidotes/therapeutic use ; Bridged Compounds/*poisoning ; Random Allocation ; Rodenticides/*poisoning ; Unithiol/therapeutic use ; gamma-Aminobutyric Acid/*administration & dosage ; gamma-Aminobutyric Acid/therapeutic use

Animals ; Anticonvulsants ; therapeutic use ; Humans ; Receptors, GABA ; genetics ; metabolism ; Seizures ; drug therapy ; genetics ; metabolism ; gamma-Aminobutyric Acid ; metabolism

AIMTo study the mechanism of protective effect of GABA against hypoxic injury in rat hippocampal slices.

METHODSThe hippocampal slices from adult rats and extracellular recording technique were used to observe the effect of GABA on the evoked population spikes in rat hippocampal slices after hypoxia in vitro.

RESULTSGABA can significantly delay the disappearance of PV, but have no effect on PS. When the receptor antagonist of GABA (bicuculline) and the inhibitor of Cl- channel (NPPB) were given, the protect effect could be suppressed.

CONCLUSIONGABA increases hypoxic tolerance of hippocampal slices. The mechanism of the effect of GABA may be involved in the elevation of chloride influx through GABA receptor.

Animals ; Chloride Channels ; physiology ; Evoked Potentials ; Hippocampus ; physiopathology ; Hypoxia ; drug therapy ; physiopathology ; In Vitro Techniques ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Wistar ; gamma-Aminobutyric Acid ; therapeutic use

BACKGROUNDGabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model.

METHODSGabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0 - 4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKII were quantified by reverse-transcriptional polymerase chain reaction and Western blotting.

RESULTSThe analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKII and phosphorylated CaMKII in CCI rats.

CONCLUSIONThe analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKII in the spinal cord.

Amines ; therapeutic use ; Analgesics ; therapeutic use ; Animals ; Blotting, Western ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Cyclohexanecarboxylic Acids ; therapeutic use ; Male ; Neuralgia ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; therapeutic use

OBJECTIVETo study the changes in plasma substance P (SP) and calcitonin gene-related peptide (CGRP) levels in children with acute asthma before and after gamma-aminobutyric acid (GABA) treatment.

METHODSSeventy-five children with asthma were randomly assigned to GABA treatment (n=36) and control groups (n=39). Both groups were given conventional treatment for asthma. Besides the conventional treatment, the treatment group was administered with oral GABA (25-30 mg/kg•d). Plasma content of SP and CGRP was measured using ELISA before treatment and after remission.

RESULTSThere were no significant differences in plasma content of SP and CGRP between the GABA treatment and control groups (P＞0.05) before treatment. Plasma content of SP and CGRP in the GABA treatment group was significantly lower than the control group (SP: 57±15 pg/mL vs 127±12 pg/mL; CGRP: 23±10 pg/mL vs 42±8 pg/mL) after remission (P<0.01). Plasma content of SP and CGRP after remission was significantly lower than before treatment (P<0.01) in both groups. There was a significantly positive correlation between plasma SP and CGRP content in asthmatic children (r=0.792, P<0.01).

CONCLUSIONSGABA can significantly decrease plasma levels of SP and CGRP in children suffering from acute asthma.

Asthma ; blood ; drug therapy ; Calcitonin Gene-Related Peptide ; blood ; Child ; Child, Preschool ; Female ; Humans ; Male ; Substance P ; blood ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

The article reviewed clinical studies on painful diabetic peripheral neuropathy (PDPN) treated by integrative medicine. PDPN, a common complication of diabetes mellitus, which could severely influence patients' quality of life. The keystone and difficulty of PDPN treatment is to relieve pain. Tricyclic anti-depressants are the firstline agents for neuropathic pain but with obvious adverse reactions. Antiepileptic drugs and capsicin can relieve PDPN with less adverse reactions. In recent years, lots of report of clinical studies on DPN treated by TCM or integrative medicine were issued, but those pertinent to PDPN were seldom. Only the papers with independent statistical analysis on effect of pain relieving were selected to review in this article, and the authors presumed that it is feasible to treat PDPN with integrative medicine.
Amines ; therapeutic use ; Amitriptyline ; therapeutic use ; Analgesics ; therapeutic use ; Animals ; Antidepressive Agents, Tricyclic ; therapeutic use ; Blood Glucose ; metabolism ; Cyclohexanecarboxylic Acids ; therapeutic use ; Diabetic Neuropathies ; complications ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; drug therapy ; etiology ; Pain Measurement ; Phytotherapy ; Triazines ; therapeutic use ; gamma-Aminobutyric Acid ; therapeutic use

OBJECTIVETo observe the effect of Dahuang Zhechong Pill (DZP) on the content of amino acids in hippocampal tissue of model rats of ischemic cerebral hemorrhage (ICH).

METHODSCollagenase and heparin were injected into caudate nucleus to establish ICH rat model. The content of glutamic acid (Glu), aspartic acid (Asp) and gamma-aminobutyric acid (GABA) in hippocampal tissue was detected by anti-phase high-performance liquid chromatographic fluorimetry to observe the effect of DZP on the content of amino acids in brain tissue.

RESULTSThree days after modeling, the content of Glu, Asp and GABA was significantly higher in the model group than those in the sham-operation and the normal control group (P < 0.05), for Glu 15.2926 +/- 4.2429 micromol/g vs 8.0057 +/- 1.1227 micromol/g and 8.5040 +/- 1.7794 micromol/g, for Asp 3.6384 +/- 3.1021 micromol/g vs 1.4986 +/- 0.4174 micromol/g and 1.2669 +/- 0.4695 micromol/g, and for GABA 0.3859 +/- 0.1846 micromol/g vs 0.1829 +/- 0.04665 micromol/g and 0.1770 +/- 0.0472 micromol/g. The content of Glu (9.0550 +/- 1.7195 micromol/g), Asp (1.8085 +/- 0.6862 micromol/g) and GABA (0.1993 +/- 0.0424 micromol/g) in hippocampal tissue in the DZP group was reduced significantly, as compared with that in the model group (P <0.05).

CONCLUSIONDZP could reduce the release of excitatory amino acids (EAA-Glu, ASP) to balance EAA/inhibitory amino acid (IAA), so as to relieve ICH-induced brain injury.

Amino Acids ; metabolism ; Animals ; Aspartic Acid ; metabolism ; Cerebral Hemorrhage ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Glutamic Acid ; metabolism ; Hippocampus ; metabolism ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo explore the analgesia of oxymatrine (OMT) affecting high voltage-dependent calcium channels (HVDCCs) and GABA release under neuropathic pain condition.

METHODSTotally 66 C57BL/6 mice were randomly divided into the sham-operation group, the model group, and the OMT group, 22 in each group. Neuropathic pain models were established by partial sciatic nerve ligation (PSNL). Hind paw plantar mechanical response threshold (MWT) was measured by up-and-down method with Von-Frey filament. mRNA expression of HVDCCs in brains and spinal cords was detected with Real-time PCR and concentration of GABA was determined using ELISA kit.

RESULTSCompared with day 0, the left hind paw MWTwas decreased on day 7, 10, and 14 in the model group (P < 0.05). Compared with the sham-operation group, the left hind paw MWT was significantly reduced in the model group on day 7 (P < 0.05). The MWT of PSNL ipsilateral hind paw was decreased on day 7 before OMT administration, when compared with day 0 (P < 0.05), and increased after OMT administration (P < 0.05). Compared with the sham-operation group, mRNA levels of Cav1.2, Cav1.3, Cav2.1, and Cav2.3 in brain tissues were increased and those of Cav2.2 were decreased significantly in the model group (P < 0.05). In spinal cord tissues, mRNA levels of Cav1.2 and Cav1.3 were increased, but those of Cav2.1, Cav2.2, and Cav2. 3 were decreased significantly in the model group, when compared with those of the sham-operation group (P < 0.05). Compared with the model group, mRNA levels of Cavl.2, Cavl.3, Cav2.1, and Cav2. 3 in brain tissues were decreased, and those of Cav2.2 were increased significantly in the OMT group (P < 0.05). In spinal cord tissues of the OMT group, mRNA levels of Cav1.3 decreased and those of Cav2.1, Cav2.2, and Cav2.3 increased significantly with statistical difference, when compared with those of the model group (P < 0.05). Compared with the sham-operation group, GABA levels in brain tissues decreased in the model group (P < 0.05). Compared with the model group, GABA levels in brain tissues increased in the OMT group (P < 0.05). There was no statistical difference in GABA levels of spinal cord tissues among these groups (P > 0.05).

CONCLUSIONSOMT had analgesic effect on neuropathic pain, which might be probably related to HVDDCs. Cav2.2 might directly affect GABA release.

Alkaloids ; pharmacology ; therapeutic use ; Analgesia ; methods ; Animals ; Calcium ; Calcium Channels ; drug effects ; metabolism ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Neuralgia ; drug therapy ; Pain Management ; Quinolizines ; pharmacology ; therapeutic use ; Spinal Cord ; metabolism ; gamma-Aminobutyric Acid

To explore new agents of gamma-aminobutyric acid (GABA) derivatives with more potent antiepileptic activity, a series of 4-(2-acetoxybenzoylamino) butyramide derivatives were designed and synthesized. All of the novel compounds (5a-51) were synthesized from GABA as starting material, and their structures were confirmed with IR, 1H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that all target compounds displayed strong antiepileptic activities and were worth for further study. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyramide derivatives was also discussed preliminarily.
4-Aminopyridine ; Amides ; chemical synthesis ; chemistry ; therapeutic use ; Animals ; Anticonvulsants ; chemical synthesis ; chemistry ; therapeutic use ; Epilepsy ; chemically induced ; drug therapy ; Female ; Male ; Mice ; Molecular Structure ; Random Allocation ; Structure-Activity Relationship ; gamma-Aminobutyric Acid ; chemistry

A series of 4-(2-acetoxybenzoylamino) butyrate derivatives were designed and synthesized. All of the novel 12 compounds (7a-7k) were synthesized from gamma-aminobutyric acid (1) as starting material, and their structures were confirmed with IR, 1H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that most of these title compounds possessed antiepileptic activity. Compounds 7i-7k displayed strong antiepileptic activity and are worth for further development. Compounds 4, 7d-7h showed moderate antiepileptic activity. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyrate derivatives is also discussed preliminarily.
4-Aminopyridine ; Animals ; Anticonvulsants ; chemical synthesis ; chemistry ; therapeutic use ; Butyrates ; chemical synthesis ; chemistry ; therapeutic use ; Drug Design ; Epilepsy ; chemically induced ; drug therapy ; Female ; Lethal Dose 50 ; Male ; Mice ; Molecular Structure ; Random Allocation ; Structure-Activity Relationship ; gamma-Aminobutyric Acid ; chemistry